Postpartum NSAIDS and Maternal Hypertension

Preeclampsia Clinical Trial

Official title:

Effect of Non-steroidal Anti-inflammatory Use on Blood Pressure in Women With Hypertensive Disorders of Pregnancy: A Randomized Open Label Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03824119
• Other study ID #: HS-17-00959
• Status: Recruiting
• Phase: Phase 4
• Start date: December 11, 2018
• Est. completion date: December 11, 2022

Study information

• Verified date: November 2020
• Source: University of Southern California
• Contact: Elizabeth Sasso, MD
• Phone: (323)409-3306
• Email: elizabeth.sasso[@]med.usc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Previous studies have suggested that NSAID use causes an increase in blood pressure. Further, blood pressure elevation has been noted in women with pregnancy related hypertensive disease during the postpartum period. NSAIDs remain part of standard postpartum care in women with hypertensive disease. The objective of this study is to determine whether postpartum standard care withholding NSAID use is associated with a clinically significant reduction in postpartum hypertension in women with pregnancy induced hypertension. The investigators hypothesize that women with pregnancy induced hypertensive disease will be half as likely to have blood pressure elevation of 150/100 mmHg in the first 24 hours postpartum.

This study is an open label randomized trial of women with antepartum hypertension. Women will be randomized to receive standard postpartum care or standard postpartum care without NSAIDs. Blood pressure measurements and patient outcomes will be recorded. The study period will begin at the time of delivery and will end at the time of hospital discharge.

Description:

The objective of this study is to determine whether the withholding of NSAID use is associated with a clinically significant decrease in postpartum hypertension in women with antepartum hypertension. The investigators are interested in whether the use of NSAIDs elevates blood pressure to greater than or equal to 150/100 mmHg (by either systolic or diastolic parameters) more frequently in hypertensive women. The investigators hypothesize that among participants with hypertensive disease associated with pregnancy, those who have NSAIDs withheld from standard postpartum care (experimental arm) will be half as likely to have an increase of blood pressure of 150/100 mmHg in the first 24 hours postpartum compared to participants receiving standard care that includes NSAIDs (control arm).

This trial is a randomized, open label study investigating the effect of NSAID use on blood pressure during the immediate postpartum period in women with chronic hypertension (cHTN) or pregnancy induced hypertension (PIH). The experimental group in this study will be women randomized to withholding NSAIDs during the study period, as women with hypertension routinely receive NSAIDs postpartum. Women with a diagnosis of pregnancy induced hypertension [gestational hypertension (gHTN), preeclampsia, superimposed preeclampsia, ] or cHTN will be enrolled antepartum and will be separated into two groups by the route of delivery: vaginal vs. cesarean delivery. Participants in the control arm will be assigned to receive standard care, which includes NSAIDs (ketorolac, ibuprofen) and participants in the experimental arm will be assigned to receive standard care with NSAIDs withheld in the postpartum period for the duration of hospitalization. The intervention period will last approximately 2-4 days and will conclude at the time of hospital discharge.

Blood pressure measurements will be obtained and recorded routinely in the postpartum period until hospital discharge. More frequent measurements may be performed in the event of severe blood pressure elevations at the discretion of the provider and treating clinical team. Complete Blood Count (CBC) on postpartum Day 1 will be performed as part of standard care. Additional laboratory evaluations will be performed at the discretion of the provider. In addition to blood pressure measurement, pain scale scores will be recorded daily using a Numeric Pain Scale Score. Initiation of anti-hypertensive medication, severe hypertension (BP 160/110 mmHg), treatment with magnesium sulfate and adverse maternal outcomes (cerebrovascular accident, congestive heart failure, pulmonary edema, eclamptic seizure, death) will be documented and abstracted from the medical record.

A power calculation to estimate the appropriate number of subjects needed to detect a difference of 30% in the primary outcome, with an alpha level of 0.05 and 80% power demonstrates that approximately 100 subjects per group (50 in the experimental group and 50 in the control group) will be needed for each delivery route tested (vaginal and cesarean).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 11, 2022
• Est. primary completion date: December 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women 18 years or older delivering at LAC/USC Hospital

• Delivery occurring at or after 20 weeks gestation

• Diagnosis of antenatal hypertensive disorder: gestational hypertension, preeclampsia without severe features, preeclampsia with severe features, superimposed preeclampsia, eclampsia, chronic hypertension

Exclusion Criteria:

• HELLP Syndrome

• Renal dysfunction (Serum Creatinine >1.1 in current pregnancy)

• Known liver disease

• Low platelet count (<50,000 during hospital admission)

• Known sensitivity or allergy to ibuprofen or acetaminophen

• Use of therapeutic doses of anticoagulation

• Postpartum hemorrhage requiring blood transfusion

• Neonate with platelet disorder or thrombocytopenia in breastfeeding mother

Related Conditions & MeSH terms

• Chronic Hypertension in Obstetric Context
• Gestational Hypertension
• Hypertension
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia
• Preeclampsia
• Superimposed Preeclampsia

Intervention

Drug:
• Ibuprofen 600 mg
Standard postpartum care (including administration of NSAIDs)

Other:
• Standard Postpartum Care without NSAIDs
NSAID administration will be withheld from this group.

Locations

Country	Name	City	State
United States	LA County Hospital/University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

References & Publications (11)

American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-31. doi: 10.1097/01.AOG.0000437382.03963.88. — View Citation

Curhan GC, Willett WC, Rosner B, Stampfer MJ. Frequency of analgesic use and risk of hypertension in younger women. Arch Intern Med. 2002 Oct 28;162(19):2204-8. — View Citation

Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med. 1994 Aug 15;121(4):289-300. — View Citation

Makris A, Thornton C, Hennessy A. Postpartum hypertension and nonsteroidal analgesia. Am J Obstet Gynecol. 2004 Feb;190(2):577-8. — View Citation

Pope JE, Anderson JJ, Felson DT. A meta-analysis of the effects of nonsteroidal anti-inflammatory drugs on blood pressure. Arch Intern Med. 1993 Feb 22;153(4):477-84. — View Citation

Schoenfeld A, Freedman S, Hod M, Ovadia Y. Antagonism of antihypertensive drug therapy in pregnancy by indomethacin? Am J Obstet Gynecol. 1989 Nov;161(5):1204-5. — View Citation

Sibai BM. Etiology and management of postpartum hypertension-preeclampsia. Am J Obstet Gynecol. 2012 Jun;206(6):470-5. doi: 10.1016/j.ajog.2011.09.002. Epub 2011 Sep 16. Review. — View Citation

Vigil-De Gracia P, Solis V, Ortega N. Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study. J Matern Fetal Neonatal Med. 2017 Jun;30(11):1279-1282. doi: 10.1080/14767058.2016.1210599. Epub 2016 Aug 2. — View Citation

Viteri OA, England JA, Alrais MA, Lash KA, Villegas MI, Ashimi Balogun OA, Chauhan SP, Sibai BM. Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in Women With Preeclampsia With Severe Features. Obstet Gynecol. 2017 Oct;130(4):830-835. doi: 10.1097/AOG.0000000000002247. — View Citation

Walters BN, Thompson ME, Lee A, de Swiet M. Blood pressure in the puerperium. Clin Sci (Lond). 1986 Nov;71(5):589-94. — View Citation

Wasden SW, Ragsdale ES, Chasen ST, Skupski DW. Impact of non-steroidal anti-inflammatory drugs on hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014 Oct;4(4):259-63. doi: 10.1016/j.preghy.2014.06.001. Epub 2014 Jul 11. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with blood pressure elevation	Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above	24 hours postpartum
Secondary	Proportion of participants with blood pressure elevation	Incidence of Systolic Blood Pressure of 150 mmHg or Diastolic Blood Pressure of 100 mmHg or above	48, 72 and 96 hours postpartum
Secondary	Number of participants with eclamptic Seizure	Documented occurrence of new onset generalized tonic-clonic seizure(s) or coma in a woman with preeclampsia	Through study completion, up to 6 weeks postpartum
Secondary	Number of participants with stroke	New onset neurologic deficit associated with neuroimaging (CT scan or MRI) evidence of brain infarction or bleeding	Through study completion, up to 6 weeks postpartum
Secondary	Initiation of anti-hypertensive medication	Provider documentation of initiation of anti-hypertensive medication (e.g. nifedipine, labetalol)	Randomization through hospital discharge, an average of 3-7 days
Secondary	Pain numerical rating scale (NRS) score	Numerical pain scale score 0-10; 0= no pain and 10=worst possible pain; total score reported	Randomization through hospital discharge, measured daily, an average of 3-7 days
Secondary	Number of participants with renal failure	Creatinine >1.1 or doubled	Through study completion, up to 6 weeks postpartum
Secondary	Number of participants with pulmonary edema	Evidence of lung infiltrates on chest radiograph or CT scan	Through study completion, up to 6 weeks postpartum
Secondary	Number of participants who die		From the date of randomization through date of death from any cause, assessed up to 6 weeks postpartum
Secondary	Length of hospital stay	Number of days from delivery to hospital discharge	Through hospital discharge, an average of 3-7 days